Negative interactions determine Clostridioides difficile growth in synthetic human gut communities.
Mol Syst Biol
; 17(10): e10355, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34693621
ABSTRACT
Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Clostridioides difficile
/
Infecções por Clostridium
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Microbioma Gastrointestinal
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos